Azathioprine

Azathioprine is an immunosuppressive antimetabolite that lowers the body's immune system used to prevent the body from rejecting a transplanted kidney. Azathioprine is also used to treat symptoms of rheumatoid arthritis.

Azathioprine is available under the following different brand names: Azasan, and Imuran.

Dosage Forms and Strengths

Capsule

• 50 mg
• 75 mg
• 100 mg

Powder for injection

• 100 mg/vial

Dosage Considerations – Should be Given as Follows:

Kidney Transplantation

• Prevention of transplant rejection
• 3-5 mg/kg/day intravenously/orally initially on day of transplant or 3 days before transplant (rare)
• Maintenance: 1-3 mg/kg/day intravenously/orally

Rheumatoid Arthritis

• 1 mg/kg/day intravenously/orally initially in single daily dose or divided every 12 hours; may be increased by 0.5 mg/kg/day after 6-8 weeks, then by 0.5 mg/kg/day every 4 weeks; not to exceed 2.5 mg/kg/day
• Maintenance: Reduce daily dose by 0.5 mg/kg every 4 weeks until lowest effective dosage is reached

Transplantation, Pediatric (Off-label)

• Prevention of transplant rejection
• 3-5 mg/kg/day intravenously/orally initially on day of transplant or 3 days before transplant (rare)
• Maintenance: 1-3 mg/kg/day intravenously/orally

Lupus Nephritis (Off-label)

• Induction and maintenance therapy for lupus nephritis (2012 American College of Rheumatology guidelines)
• Adult: 2 mg/kg/day orally with or without low-dose corticosteroids
• Induction and maintenance therapy for lupus nephritis (2012 American College of Rheumatology guidelines)
• Children under 12 years: Safety and efficacy not established
• Children over 12 years: 2 mg/kg/day orally with or without low-dose corticosteroids

Crohn's Disease (Off-label)

• Maintenance, remission, or reduction of steroid
• 2-3 mg/kg orally once daily

Ulcerative Colitis (Off-label)

• Maintenance, remission, or reduction of steroid
• 1.5-2.5 mg/kg orally once daily

Chronic Refractory Thrombocytopenic Purpura (Off-label)

• 1-2 mg/kg orally once daily to maximum daily dose of 150 mg for at least 3-6 months before typical response is observed
• Dosing considerations
  • Lower dosage (100 mg/day) is reported effective in some patients
  • Longer treatment duration (up to 84 months) is reported in some patients

Juvenile Idiopathic Arthritis

• 1 mg/kg/day intravenously/orally initially in single daily dose or divided every 12 hours; may be increased by 0.5 mg/kg/day after 6-8 weeks, then by 0.5 mg/kg/day every 4 weeks; not to exceed 2.5 mg/kg/day
• Maintenance: Reduce daily dose by 0.5 mg/kg every 4 weeks until lowest effective dosage is reached

Common side effects of azathioprine include:

• Low white blood cell count (leukopenia)
• Infection
• Lymphoma

Other side effects of azathioprine include:

• Abdominal pain
• Bacterial, fungal, protozoan, viral infections
• Bone marrow suppression
• Diarrhea
• Fever
• Hair loss
• Joint Pain
• Liver damage
• Loss of appetite
• Low platelet count (thrombocytopenia)
• Macrocytic anemia
• Muscle pain
• Nausea or vomiting
• Pale, oily feces (fat in stool)
• Skin cancer
• Skin rash
• Sweet syndrome (acute febrile neutrophilic dermatosis)
• Upset stomach

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

• Severe interactions of azathioprine include:
  • febuxostat
• Azathioprine has serious/ interactions with at least 67 different drugs.
• Azathioprine has moderate interactions with at least 42different drugs.
• Mild interactions of azathioprine include:
  • sulfamethoxazole

This information does not contain all possible interactions or adverse effects. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns or for more information about this medicine.

Warnings

Chronic immunosuppression with this purine antimetabolite increases neoplasia risk, mutagenic risk, and hematologic toxicities.

Reported malignancies include post-transplant lymphoma and hepatosplenic T-cell lymphoma (HSTCL) in patients with inflammatory bowel disease.

Prescribing physicians should be familiar with mutagenic potential and with possible hematologic toxicities.

This medication contains azathioprine. Do not take Azasan or Imuran if you are allergic to azathioprine or any ingredients contained in this drug.

Contraindications

• Hypersensitivity
• Narrow-angle glaucoma
• Administration concomitantly with or within 14 days of monoamine oxidase inhibitor (MAOI) therapy; risk of potentially fatal reaction, including hyperthermia, myoclonus, altered mental status, and neuroleptic malignant syndrome (NMS)-like symptoms
• Pheochromocytoma: Serious reactions, including elevated blood pressure and tachyarrhythmia, have been reported in patients with current or previous pheochromocytoma
• Severe cardiovascular disorders where condition would deteriorate because blood pressure increases by 15-20 mm Hg or heart rate increases by 20 beats/minute; risk is greater in poor CYP2D6 metabolizers

Effects of Drug Abuse

• No information available

Short-Term Effects

• See "What Are Side Effects Associated with Using Azathioprine?"

Long-Term Effects

• Long-term use increases risk of neoplasia.
• See "What Are Side Effects Associated with Using Azathioprine?"

Cautions

• Long-term use increases risk of neoplasia.
• Increased risk of infection and hepatotoxicity.
• Cases of JC virus-associated infection resulting in progressive multifocal leukoencephalopathy (PML), sometimes fatal, reported in patients treated with immunosuppressants, including azathioprine.
• Hepatosplenic T-cell lymphoma:
  • Rare postmarketing cases of HSTCL reported primarily in adolescent and young adult patients with Crohn disease and ulcerative colitis treated with tumor necrosis factor (TNF) blockers.
  • Reports have also included 1 patient being treated for psoriasis and 2 patients being treated for rheumatoid arthritis.
  • HSTCL is an aggressive, rare type of T-cell lymphoma that is usually fatal.
  • Most reported cases with TNF blockers have occurred in context of concomitant treatment with azathioprine or 6-mercaptopurine (6-MP), though cases have been reported with azathioprine or 6-MP alone.
  • In the FDA Adverse Event Reporting System (AERS) database, the literature, and the HSTCL Cancer Survivors' Network, HSTCL cases have been identified in association with the following drugs: infliximab (20), etanercept (1), adalimumab (2), infliximab/adalimumab (5), certolizumab (0), golimumab (0), azathioprine (12), 6-MP (3).

Pregnancy and Lactation

• Use azathioprine during pregnancy only in LIFE-THREATENING emergencies when no safer drug is available. There is positive evidence of human fetal risk.
• Azathioprine is excreted at low levels in breast milk; use is not recommended while breastfeeding.